Efficacy and Tolerability of Alitretinoin for Chronic Hand Eczema Under Daily Practice Conditions: Results of the TOCCATA Open Study Comprising 680 Patients

Diepgen, Thomas L.; Pfarr, Egon; Zimmermann, Thomas

doi:10.2340/00015555-1256

Cited by 66 publications

(86 citation statements)

References 19 publications

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“…Taken together, our results confirm the good clinical efficacy of oral alitretinoin seen both in the clinical development program and in clinical practice [32]. Moreover, our data indicates that 9- cis- RA is a potent modulator of inflammatory processes concerning the T cell but also the B cell compartment in patients with CHE.…”

Section: Discussionsupporting

confidence: 74%

Immunomodulation in Patients with Chronic Hand Eczema Treated with Oral Alitretinoin

Schindler¹,

Drozdenko²,

Kühl³

et al. 2014

Int Arch Allergy Immunol

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Background: Oral alitretinoin (9-cis-retinoic acid; 9-cis-RA) has shown clinical efficacy in patients with chronic hand eczema (CHE). Herein, we investigated the impact of oral 9-cis-RA on the local and systemic immune response in patients with CHE. Methods: Twenty patients with CHE were treated with oral alitretinoin (10 or 30 mg/day) for at least 24 weeks. Blood samples were taken for flow cytometry, and serum samples were assessed by ELISA to determine immunoglobulin (Ig) levels. Skin biopsies from lesional skin were evaluated immunohistochemically. Results: Upon 9-cis-RA treatment, improvement of the CHE was observed in all patients. A significant decrease in plasmablasts in the peripheral blood and a significant reduction of serum IgE levels were determined. Furthermore, we detected a significant reduction of CD4+ cells and regulatory T cells in the peripheral blood upon treatment. By contrast, these cell subsets were significantly increased in the affected skin. Cytokine analysis of activated CD154-positive T cells showed a reduction of interleukin (IL)-17 but not of IL-4 or IFN-γ production. Conclusions: Overall, our data indicate a disease-modifying effect of 9-cis-RA, including a systemic decrease in IL-17-positive cells, but decreased serum IgE and CD23 expression. The increased frequency of FoxP3-positive cells in the skin upon treatment may suggest a mechanism by which hand eczema is therapeutically targeted by 9-cis-RA, but this will need to be proven in the future studies.

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Section: Discussionsupporting

confidence: 74%

Immunomodulation in Patients with Chronic Hand Eczema Treated with Oral Alitretinoin

Schindler¹,

Drozdenko²,

Kühl³

et al. 2014

Int Arch Allergy Immunol

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“…Retinoids have been used to successfully treat eczema in a number of studies 42, 43, 44. Typically, around 50% of patients respond to retinoid treatment 42 .…”

Section: Discussionmentioning

confidence: 99%

“…Retinoids have been used to successfully treat eczema in a number of studies 42, 43, 44. Typically, around 50% of patients respond to retinoid treatment 42 . Although the immunosuppressive properties of retinoids are cited as the cause of recovery, another reason could be the reduction of RAPTOR expression and subsequent increase in filaggrin expression and processing.…”

Section: Discussionmentioning

confidence: 99%

A mechanistic target of rapamycin complex 1/2 (mTORC1)/V-Akt murine thymoma viral oncogene homolog 1 (AKT1)/cathepsin H axis controls filaggrin expression and processing in skin, a novel mechanism for skin barrier disruption in patients with atopic dermatitis

Naeem¹,

Tommasi²,

Callebaut

et al. 2017

Journal of Allergy and Clinical Immunology

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BackgroundFilaggrin, which is encoded by the filaggrin gene (FLG), is an important component of the skin's barrier to the external environment, and genetic defects in FLG strongly associate with atopic dermatitis (AD). However, not all patients with AD have FLG mutations.ObjectiveWe hypothesized that these patients might possess other defects in filaggrin expression and processing contributing to barrier disruption and AD, and therefore we present novel therapeutic targets for this disease.ResultsWe describe the relationship between the mechanistic target of rapamycin complex 1/2 protein subunit regulatory associated protein of the MTOR complex 1 (RAPTOR), the serine/threonine kinase V-Akt murine thymoma viral oncogene homolog 1 (AKT1), and the protease cathepsin H (CTSH), for which we establish a role in filaggrin expression and processing. Increased RAPTOR levels correlated with decreased filaggrin expression in patients with AD. In keratinocyte cell cultures RAPTOR upregulation or AKT1 short hairpin RNA knockdown reduced expression of the protease CTSH. Skin of CTSH-deficient mice and CTSH short hairpin RNA knockdown keratinocytes showed reduced filaggrin processing, and the mouse had both impaired skin barrier function and a mild proinflammatory phenotype.ConclusionOur findings highlight a novel and potentially treatable signaling axis controlling filaggrin expression and processing that is defective in patients with AD.

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“…The treatment response rates defined as “clear” or “almost clear” by PGA assessment were 40%, 28%, and 17%, respectively . In another non‐interventional, observational open study, TOCCATA, which admitted concomitant use of topical corticosteroids, 680 CHE patients treated with alitretinoin were monitored up to 24 weeks and 56.7% of patients achieved a PGA rating of “clear” or “almost clear.”…”

Section: Discussionmentioning

confidence: 99%

Efficacy of alitretinoin depending on the concomitant use of topical corticosteroids in chronic hand eczema patients

Cheon

Kim

et al. 2019

The Journal of Dermatology

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Alitretinoin is the only systemic agent approved for the treatment of severe chronic hand eczema (CHE) unresponsive to potent topical corticosteroids. Clinical trials have shown the efficacy of oral alitretinoin with topical emollients for CHE treatment, but most studies have failed to reach a therapeutic success rate of 50%. Reasonably, we thought it would be more effective to combine topical corticosteroids with oral alitretinoin, but the concomitant use of topical corticosteroids has not been studied yet. One‐hundred and seven Korean patients diagnosed with CHE were recruited. The participants were divided into two groups depending on the concomitant use of topical corticosteroids. Comparative analysis was performed between the combined therapy (alitretinoin and topical corticosteroids) and monotherapy groups (alitretinoin only) by using physician global assessment (PGA), patient's global assessment (PaGA), modified total lesion symptom score (mTLSS), and recurrence rates. The combined therapy group showed a significantly higher treatment success rate than the alitretinoin monotherapy group for all efficacy parameters (PGA: P < 0.001, PaGA: P < 0.001, mTLSS changes: P < 0.001), but there was no significant difference in recurrence rates between the groups (P = 0.266). Combined use of topical corticosteroids is recommended for CHE patients being treated with oral alitretinoin due to clinically rapid and superior effectiveness.

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Efficacy and Tolerability of Alitretinoin for Chronic Hand Eczema Under Daily Practice Conditions: Results of the TOCCATA Open Study Comprising 680 Patients

Cited by 66 publications

References 19 publications

Immunomodulation in Patients with Chronic Hand Eczema Treated with Oral Alitretinoin

Immunomodulation in Patients with Chronic Hand Eczema Treated with Oral Alitretinoin

A mechanistic target of rapamycin complex 1/2 (mTORC1)/V-Akt murine thymoma viral oncogene homolog 1 (AKT1)/cathepsin H axis controls filaggrin expression and processing in skin, a novel mechanism for skin barrier disruption in patients with atopic dermatitis

Efficacy of alitretinoin depending on the concomitant use of topical corticosteroids in chronic hand eczema patients

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